A major breakthrough in the treatment of psoriasis has been the discovery that a regimen involving systemic treatment with a psoralen derivative such as orally administered 8-methoxypsoralen followed in two to five hours by exposure of the subject to ultraviolet A light resulted in an extremely high clearing response rate of the psoriatic lesions.
Regimens which have been utilized in a multi-center clinical trial of this treatment procedure involve two to four times per week treatments during the clearing phase which ranged from an average of 20 to 77 days depending on treatment frequency and patient's skin color. Upon complete clearing the subject received maintenance treatments consisting initially of one to three treatments per week which gradually tapered to about once a month.
The oral dosage levels used in the aforesaid studies were based on the patient's weight: up to 50 kg. body weight, 20 mg.; 51-65 kg., 30 mg.; 66-80 kg., 40 mg.; greater than 80 kg., 50 mg. Total energy applied to the subjects using ultraviolet A light exposure during the clearing phase therapy ranged from an average of approximately 90 Joules/cm.sup.2 to over 200 Joules/cm.sup.2 depending at least in part on the drug dosage regimen utilized.
Further specific details concerning the methodology of the PUVA treatment for psoriasis are to be found in U.S. Patent Application Ser. No. 618,152, filed Sept. 30, 1975, entitled "Process for Artifically Inducing a Natural Tan of the Human Body and Alleviating Psoriasis", inventors Thomas B. Fitzpatrick and John A. Parrish.
In U.S. Patent Application Ser. No. 823,257 filed Aug. 10, 1977, entitled "Process to Produce 8-Methoxypsoralen and Derivatives Thereof", inventors P. N. Confalone et al., there are disclosed analogs of 8-methoxypsoralen which exhibit potent photosensitizing activity which is thought to be linked to antipsoriatic activity. Such analogs are 2-methyl-9-methoxypsoralen, 5-methyl-9-methoxypsoralen and 2,5-dimethyl-9-methoxypsoralen.
Additional psoralen derivatives exhibiting potent photobiological activity are disclosed by Issacs et al., Biochemistry, 16, 1058 (1977). Particular new psoralen derivatives disclosed include 4'-hydroxymethyl-,4'-methoxymethyl-, and 4'-amino-methyl-4,5',8-trimethylpsoralen. Furthermore, D. Averback has reported recently that a newly synthesized psoralen 3-carbethoxypsoralen is a potent photoactive derivative. See VII International Congress on Photobiology Aug. 29-Sept. 3, 1976) at page 137.
Anti-psoriatic polyene compounds are known in the prior art. Examples of such disclosures are as follows:
Belgian Pat. No. 833,784 (Derwent 26452X)--Phenyl-tetraene compounds such as 9-phenyl-3,7-dimethyl-nona-2,4,6,8-tetraen-1-oates.
Belgian Pat. No. 818,648 (Derwent 14330W)--Fused carbocyclic-substituted polyenes such as 9-(8-methoxy-6,7-dimethyl-tetralin-5-yl)-3,7-nona-2,4,6,8-tetraen-1-oic acid and its esters as well as 2,3-dimethyl-naphthalene and pentamethylchromanyl derivatives.
Netherlands Pat. No. 7404324 (Derwent 73782V)--Polyene compounds such as 9-(4-methoxy-2,3,6-trimethylphenyl)-3,7-dimethyl-nona-2,4,6,8-tetraenic-1- carboxylic acid.
U.S. Pat. No. 3,931,257 (Derwent 05421X)--Substituted nona-2,4,6-trienoic acid derivatives such as 3,7-dimethyl-9-(2,6,6-trimethyl-cyclohex- 1-en-1-yl)-nona-2,6,8-trien-1-oic acid methyl ester.
West German Pat. No. 2542600 (Derwent 32296X)--Halo substituted polyene compounds such as 3,7-dimethyl-9-(2-chloro-4-methoxy-3,5,6-trimethylphenyl)-nona-2,4,6-trien oic-1-acid, 3,7-dimethyl-9-(2,3,4,5,6-pentachlorophenyl)-nona-2,4,6-trienoic-1-acid and esters thereof.
West German Pat. No. 2542601 (Derwent 32297X)--9-Aryl polyenes such as 9-aryl-3,7-dimethyl-nona-2,6,8-trien-1-oic acids and derivatives.
West German Pat. No. 2440525 (Derwent 17939W)--Dihydro-vitamin A derivatives and analogs which are substituted in the 2- and 6-position by lower alkyl, lower alkoxy or halogen and in more than one of positions 3,4 and 5 by hydroxy, halogen, lower alkyl, lower alkenyl, lower alkoxy, lower alkenoxy, lower alkanoyloxy, amino or N-heterocyclic residue. An exemplary compound is 2-cis/trans-3,7-dimethyl-9-(2,6,6-trimethyl-1-cyclohexenyl)-nona-2,4,6-tri enoate.
West German Pat. No. 2440606 (Derwent 17953W) --Dihydrovitamin A derivatives and analogs including, for example 3,7-dimethyl-9-(2,6,6-trimethylcyclohex-1-en-1-yl)-nona-2,6,8-trien-1-oic acid, 3,7-dimethyl-9-(4-methoxy-2,3,6-trimethylphenyl)-nona-2,6,8-trien-1-oic acid and esters thereof.
Belgian Pat. No. 813002 (Derwent 74285V)--Substituted phenyl-nona-tetraenic acids, esters and amides including, for example butyl 9-(4-methoxy-2,3,6-trimethyl-phenyl)-3,7-dimethyl-nona-2,4,6,8-tetraen-1-o ate and the corresponding ethyl ester.
West German Pat. No. 2306112 (Derwent 60135V)--N-substituted thiourea derivatives of vitamin A acid.
West German Pat. No. 2300107 (Derwent 52199V)--N-substituted vitamin A acid amides.
Belgian Pat. No. 847943 (Derwent 32747Y) -- Esters and amides of all trans retinoic acid such as retinoyloxyacetamide.
U.S. Pat. No. 3,934,028 -- Use of retinoic acid analogs in the treatment of acne and psoriasis. A specific compound disclosed in 11-(2,6',6'-trimethylcyclohex-1-enyl-1')-5,9-dimethylundeca-2,4,6,8,10-pen tenoic acid.
U.S. Pat. No. 3,966,967 -- Use of vinylogs of retinoic acid to treat psoriasis and related skin disorders. A specific compound disclosed is 2,6,6-trimethyl-1-(10'-carboxy-deca-1',3',5',7',9'-pentaenyl)cyclohex-1-en e.